Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial

Burnett, A.K., Hills, R.K., Milligan, D.W., Goldstone, A.H., Prentice, A.G., McMullin, M.-F., Duncombe, A., Gibson, B. and Wheatley, K. (2010) Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. Journal of Clinical Oncology, 28(4), pp. 586-595. (doi:10.1200/JCO.2009.22.9088)

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Abstract

Purpose: To optimize treatment for younger patients with acute myeloid leukemia and high-risk myelodysplastic syndrome by comparing induction options and the number of consolidation courses and whether consolidation should include transplantation.

Patients and Methods: We randomly assigned 1,658 patients younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992 patients were randomly assigned between a total of four courses versus five courses, and 324 patients who were not good risk were randomly assigned to transplantation or chemotherapy as the final course.

Results: Complete remission (CR) was achieved in 74% of patients and CR without recovery was achieved in an additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR, relapse-free survival, relapse, or OS were seen between any of the induction randomizations except for a reduction in relapse risk (RR) on the mitoxantrone arm, which was offset by increased myelosuppression and deaths in CR. The addition of a fifth course did not improve OS and may be detrimental in older patients. Although transplantation reduced RR, it did not improve OS for the intermediate-risk group but was probably of benefit in high-risk patients.

Conclusion: Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gibson, Professor Brenda
Authors: Burnett, A.K., Hills, R.K., Milligan, D.W., Goldstone, A.H., Prentice, A.G., McMullin, M.-F., Duncombe, A., Gibson, B., and Wheatley, K.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Clinical Oncology
Journal Abbr.:J. Clin. Oncol.
ISSN:0732-183X
ISSN (Online):1527-7755

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